The proposed research on the physiology of osteoinduction has clinical and experimental objectives. The clinical objective is to prepare osteoinductive dentin and bone alloimplants for patients with jaw bone and long bone defects derived from tumors, infections, injuries, and congenital malformations. The experimental objective is to isolate and characterize the bone morphogenetic protein (BMP) in dentin and bone matrix responsible for osteoinduction. BMP is bioassayed by implantation of lyophilized samples in a muscle pouch in gelatin capsules and doubled-walled diffusion chambers of pore size as small as 0.025 microns in allogeneic rabbits, rats and mice. While there are many systems for cell-cell interactions between mesenchymal cells and uroepithelium or HeLa cells or amnion or transformed fibroblasts, only one system produces bone from interaction of mesenchymal cells with a chemically defined substratum. This system consists of interaction of mesenchymal cells or young fibroblasts with either dentin or bone or osteosarcoma matrix. In tissue culture, the product is cartilage while in vivo, bone and bone marrow. Knowledge of the physiology of the inductive matrix is applied in the preparation of a chemosterilized, autolysed antigen extracted, allogeneic (AAA) bone graft. The experimental program is to characterize the biochemical components of dentin, bone and osteosarcomas responsible for the osteoinductive response in adult rabbits, rats, and mice. The experiments are designed to separate insoluble bone morphogenetic protein (BMP) from bone matrix by melting bone collagen at 25 degress C in LiCl and to isolate soluble BMP at 37 degress C by hollow fiber ultrafiltration. Soluble BMP is characterized by chemical analyses, gel filtration, gel electrophoresis, immunophoresis, column chromatography, amino acid analyses, and amino acid sequenation. A solubilized BMP is also obtained from cortical bone matrix powder by incubation at 37 degress C in buffered solutions containing endogenous sulfhydryl enzyme inhibitors and a bone matrix glycoprotein carrier. Bone matrix BMP will be compared with a soluble BMP in the media of osteosarcoma cell cultures.